Celiac disease is an inherited, autoimmune disease in which the lining of the small intestine is damaged from eating gluten and other proteins found in wheat, barley, rye, and possibly oats. The symptoms of celiac disease can vary significantly from person to person. This is part of the reason the diagnosis is frequently delayed. For example, one person may have constipation, a second may have diarrhea, and a third may have no irregularity in stools. An endoscopy with enteroscopy, particularly of the distal small intestine which most commonly affected, reveals flattening of the villi.
Celiac disease is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 and 33-mer gliadin peptides. The transferrin receptor, CD71, is responsible for apical to basal retrotranscytosis of gliadin peptides. During this process peptide 31-49 and 33-mer peptides are protected from degradation. In patients with active celiac disease, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact peptide 31-49 and 33-mer peptides is blocked by polymeric and secretory IgA. This retrotranscytosis of secretory IgA-gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa. This may then initiate an immune response and perpetuate intestinal inflammation. These findings strongly implicate CD71 in the pathogenesis of celiac disease (Matysiak-Budnik T et al. 2008).
Treatment consists of adherence to a lifelong gluten-free diet. This allows the intestinal villi to heal. Foods, beverages, and medications that contain wheat, barley, and rye are eliminated. Wheat, rye, and barley are the grains that contain pathogenic peptides. Since wheat and barley comprise a major component of the American diet, this diet is difficult to adhere to.
Gastrointestinal symptoms in patients with symptomatic celiac disease who adhere to a gluten-free diet typically resolve within a few weeks. These patients experience the resolution of the findings of malnutrtion, improved growth with resultant normal stature, and normalization of blood and biochemical laboratory studies. Normal results from a follow-up endoscopy with biopsy several months after the diagnosis and treatment confirm the disease.
Thus, there exists a need for a therapeutic that is resistant to gastrointestinal tract degradation that is able to inhibit the symptoms of celiac disease in an afflicted subject. There also exists a need to provide such a therapeutic in a dosing form well suited for orally treating a celiac disease afflicted subject.